Examples of therapeutic drugs against the acquired immunodeficiency syndrome (AIDS) caused by an infection with the human immunodeficiency virus (HIV) include a reverse transcriptase inhibitor and a protease inhibitor. However, therapeutic effectiveness of those drugs has been lost due to the emergence of drug resistant HIV mutants (see, for example, Non-patent Document 1). Also, the polypharmacy using the combination of such drugs has such disadvantages that it requires many conditions to be observed in administration, that it is complex, that it needs many kinds of drugs to be administered, and that it causes various side effects (see, for example, Non-patent Document 2). Moreover, particularly in case of using the protease inhibitor, it is known that the probability of causing emergence and screening of the resistant strain will increase unless the administration of approximately 100% of the drugs is kept, in spite of the complex administration method and many side effects thereof (see, for example, Non-patent Document 3).
Alternatively, development of vaccine has been attempted because many viral diseases were destroyed or remarkably weakened by vaccines in the past. However, this is considered to be extremely difficult since mutations are occurred frequently in HIV (see, for example, Non-patent Document 4).
Although several kinds of compounds having an anti-HIV effect have been reported as described above, it is now strongly desired to develop a novel antiviral drug which has excellent anti-retrovirus effect, is capable of opposing to the expression of the resistance, and which has little toxicity and causes little side effect, thereby allowing a long term administration.
Chemokine is one kind of cytokine which renders chemotaxis to leukocytes, and is a secretory protein. Chemokine is classified into CXC-chemokine, CC-chemokine, C-chemokine, CX3C-chemokine according to the cysteine (Cys) sequence at N-terminal, and the total number thereof is said to be about 30. The chemokine receptor includes several sub-types. Among them, it is known that the CXCR4 to which a ligand CXC-chemokine SDF-1α binds is utilized as a coreceptor on infection to a host cell of a T cell-directive HIV (see, for example, Non-patent Document 5 and Non-patent Document 6). The HIV invades through binding of its envelope protein gp120 to the CXCR4 on the surface of a host cell. That is, the drug having antagonism against the CXCR4 is expected as an anti-HIV drug based on a novel mechanism of invasion inhibition, and there have been reported three low-molecular compounds as such drugs: AMD3100 (see, for example, Non-patent Document 7), T22 (see, for example, Non-patent Document 8), and ALX40-4C (see, for example, Non-patent Document 9).
On the other hand, it has been elucidated that the CXCR4 associates with various diseases besides HIV infection. For example, there has been reported its association with a rheumatic disease (see, for example, Patent Document 1), a cancer metastatic disease (see, for example, Non-patent Document 10), or the like.
As a therapeutic drug for such diseases, it is strongly desired to develop a novel low-molecular drug which has CXCR4 antagonism, and which has little toxicity and causes little side effect, thereby allowing a long-term administration.    [Patent Document 1] WO 00/06086    [Non-patent Document 1] Saishin Igaku, Vol. 53, No. 9, p. 2031 (1998)    [Non-patent Document 2] Nikkei Science, October, p. 29 (1998)    [Non-patent Document 3] Molecular Medicine, Vol. 36, No. 9, p. 1012 (1999)    [Non-patent Document 4] Nikkei Science, October, p. 42 (1998)    [Non-patent Document 5] Science, 272, 872 (1996)    [Non-patent Document 6] Nature, 382, 829 (1996)    [Non-patent Document 7] J. Exp. Med, 186, 1383 (1997)    [Non-patent Document 8] J. Exp. Med, 186, 1389 (1997)    [Non-patent Document 9] J. Exp. Med, 186, 1395 (1997)    [Non-patent Document 10] Nature, 410, 50 (2001)